Neuroendocrine Control of Pituitary Hormone Secretion: The molecular mechanism(s) by which steroid hormones regulate the release of hypothalmic releasing factors and thereby control the release of pituitary hormones is not well defined. Three loci for steroid hormone action have been identified: extra-hypothalamic brain nuclei, the hypothalamus, and the pituitary. Evidence from our laboratory has shown that subcellular fractions of specific brain regions are altered via steroid treatment. Thus the content and release of luteinizing hormone releasing hormone (LHRH) in hypothalamic (HYP) synaptosomes and the transport of gamma-aminobutyrate (GABA) in hippocampal (HIP) synaptosomes are changed with ovariectomy plus or minus estrogens and adrenalectomy plus or minus corticosterone respectively. We propose to continue our examination of the mechanism by which estrogens (E) inhibit or block the release of LHRH and by which glucocorticoids (G) control the activity of hippocampal neurons. HYP and HIP will be separated into neuronal and glial fractions to examine the locus of steroid action. The following will be examined: interaction of E and G with their respective receptors, the activation of RNA polymerases I and II by E and G, and the synthesis and subcellular distribution of specific proteins in response to E or G. In addition, we propose a study of the synthesis, processing, packaging and release of LHRH itself. From our previous results and those of others, we believe that cellular and subcellular fractionation of central nervous tissues known to be target sites for steroids into neurons, glia, and functional subcellular units offers the field of endocrinology unique models for the elucidation of mechanism(s) by which steroids regulate neuroendocrine systems.